Obesity and disease severity magnify disturbed microbiome-immune interactions in asthma patients

David Michalovich; Noelia Rodriguez-Perez; Sylwia Smolinska; Michal Pirozynski; David Mayhew; Sorif Uddin; Stephanie Van Horn; Milena Sokolowska; Can Altunbulakli; Andrzej Eljaszewicz; Benoit Pugin; Weronika Barcik; Magdalena Kurnik-Lucka; Ken A Saunders; Karen D Simpson; Peter Schmid-Grendelmeier; Ruth Ferstl; Remo Frei; Noriane Sievi; Malcolm Kohler; Pawel Gajdanowicz; Katrine Bækby Graversen; Katrine Lindholm Bøgh; Marek Jutel; James R Brown; Cezmi A Akdis; Edith M Hessel; Liam O'Mahony

doi:10.1038/s41467-019-13751-9

Obesity and disease severity magnify disturbed microbiome-immune interactions in asthma patients

David Michalovich, Noelia Rodriguez-Perez, Sylwia Smolinska, Michal Pirozynski, David Mayhew, Sorif Uddin, Stephanie Van Horn, Milena Sokolowska, Can Altunbulakli, Andrzej Eljaszewicz, Benoit Pugin, Weronika Barcik, Magdalena Kurnik-Lucka, Ken A Saunders, Karen D Simpson, Peter Schmid-Grendelmeier, Ruth Ferstl, Remo Frei, Noriane Sievi, Malcolm KohlerPawel Gajdanowicz, Katrine Bækby Graversen, Katrine Lindholm Bøgh, Marek Jutel, James R Brown, Cezmi A Akdis, Edith M Hessel, Liam O'Mahony^*

^*Corresponding author for this work

Research output: Contribution to journal › Journal article › Research › peer-review

91 Downloads (Pure)

Abstract

In order to improve targeted therapeutic approaches for asthma patients, insights into the molecular mechanisms that differentially contribute to disease phenotypes, such as obese asthmatics or severe asthmatics, are required. Here we report immunological and microbiome alterations in obese asthmatics (n = 50, mean age = 45), non-obese asthmatics (n = 53, mean age = 40), obese non-asthmatics (n = 51, mean age = 44) and their healthy counterparts (n = 48, mean age = 39). Obesity is associated with elevated proinflammatory signatures, which are enhanced in the presence of asthma. Similarly, obesity or asthma induced changes in the composition of the microbiota, while an additive effect is observed in obese asthma patients. Asthma disease severity is negatively correlated with fecal Akkermansia muciniphila levels. Administration of A. muciniphila to murine models significantly reduces airway hyper-reactivity and airway inflammation. Changes in immunological processes and microbiota composition are accentuated in obese asthma patients due to the additive effects of both disease states, while A. muciniphila may play a non-redundant role in patients with a severe asthma phenotype.

Original language	English
Article number	5711
Journal	Nature Communications
Volume	10
Number of pages	14
ISSN	2041-1723
DOIs	https://doi.org/10.1038/s41467-019-13751-9
Publication status	Published - 2019

Access to Document

10.1038/s41467-019-13751-9

fulltextFinal published version, 2.98 MB

Fingerprint Dive into the research topics of 'Obesity and disease severity magnify disturbed microbiome-immune interactions in asthma patients'. Together they form a unique fingerprint.

Cite this

Michalovich, D., Rodriguez-Perez, N., Smolinska, S., Pirozynski, M., Mayhew, D., Uddin, S., Van Horn, S., Sokolowska, M., Altunbulakli, C., Eljaszewicz, A., Pugin, B., Barcik, W., Kurnik-Lucka, M., Saunders, K. A., Simpson, K. D., Schmid-Grendelmeier, P., Ferstl, R., Frei, R., Sievi, N., ... O'Mahony, L. (2019). Obesity and disease severity magnify disturbed microbiome-immune interactions in asthma patients. Nature Communications, 10, [5711]. https://doi.org/10.1038/s41467-019-13751-9

Michalovich, David ; Rodriguez-Perez, Noelia ; Smolinska, Sylwia ; Pirozynski, Michal ; Mayhew, David ; Uddin, Sorif ; Van Horn, Stephanie ; Sokolowska, Milena ; Altunbulakli, Can ; Eljaszewicz, Andrzej ; Pugin, Benoit ; Barcik, Weronika ; Kurnik-Lucka, Magdalena ; Saunders, Ken A ; Simpson, Karen D ; Schmid-Grendelmeier, Peter ; Ferstl, Ruth ; Frei, Remo ; Sievi, Noriane ; Kohler, Malcolm ; Gajdanowicz, Pawel ; Graversen, Katrine Bækby ; Bøgh, Katrine Lindholm ; Jutel, Marek ; Brown, James R ; Akdis, Cezmi A ; Hessel, Edith M ; O'Mahony, Liam. / Obesity and disease severity magnify disturbed microbiome-immune interactions in asthma patients. In: Nature Communications. 2019 ; Vol. 10.

@article{b69190639a2a4424b5f372f3f5237211,

title = "Obesity and disease severity magnify disturbed microbiome-immune interactions in asthma patients",

abstract = "In order to improve targeted therapeutic approaches for asthma patients, insights into the molecular mechanisms that differentially contribute to disease phenotypes, such as obese asthmatics or severe asthmatics, are required. Here we report immunological and microbiome alterations in obese asthmatics (n = 50, mean age = 45), non-obese asthmatics (n = 53, mean age = 40), obese non-asthmatics (n = 51, mean age = 44) and their healthy counterparts (n = 48, mean age = 39). Obesity is associated with elevated proinflammatory signatures, which are enhanced in the presence of asthma. Similarly, obesity or asthma induced changes in the composition of the microbiota, while an additive effect is observed in obese asthma patients. Asthma disease severity is negatively correlated with fecal Akkermansia muciniphila levels. Administration of A. muciniphila to murine models significantly reduces airway hyper-reactivity and airway inflammation. Changes in immunological processes and microbiota composition are accentuated in obese asthma patients due to the additive effects of both disease states, while A. muciniphila may play a non-redundant role in patients with a severe asthma phenotype.",

author = "David Michalovich and Noelia Rodriguez-Perez and Sylwia Smolinska and Michal Pirozynski and David Mayhew and Sorif Uddin and {Van Horn}, Stephanie and Milena Sokolowska and Can Altunbulakli and Andrzej Eljaszewicz and Benoit Pugin and Weronika Barcik and Magdalena Kurnik-Lucka and Saunders, {Ken A} and Simpson, {Karen D} and Peter Schmid-Grendelmeier and Ruth Ferstl and Remo Frei and Noriane Sievi and Malcolm Kohler and Pawel Gajdanowicz and Graversen, {Katrine B{\ae}kby} and B{\o}gh, {Katrine Lindholm} and Marek Jutel and Brown, {James R} and Akdis, {Cezmi A} and Hessel, {Edith M} and Liam O'Mahony",

year = "2019",

doi = "10.1038/s41467-019-13751-9",

language = "English",

volume = "10",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

}

Michalovich, D, Rodriguez-Perez, N, Smolinska, S, Pirozynski, M, Mayhew, D, Uddin, S, Van Horn, S, Sokolowska, M, Altunbulakli, C, Eljaszewicz, A, Pugin, B, Barcik, W, Kurnik-Lucka, M, Saunders, KA, Simpson, KD, Schmid-Grendelmeier, P, Ferstl, R, Frei, R, Sievi, N, Kohler, M, Gajdanowicz, P, Graversen, KB, Bøgh, KL, Jutel, M, Brown, JR, Akdis, CA, Hessel, EM & O'Mahony, L 2019, 'Obesity and disease severity magnify disturbed microbiome-immune interactions in asthma patients', Nature Communications, vol. 10, 5711. https://doi.org/10.1038/s41467-019-13751-9

Obesity and disease severity magnify disturbed microbiome-immune interactions in asthma patients. / Michalovich, David; Rodriguez-Perez, Noelia; Smolinska, Sylwia; Pirozynski, Michal; Mayhew, David; Uddin, Sorif; Van Horn, Stephanie; Sokolowska, Milena; Altunbulakli, Can; Eljaszewicz, Andrzej; Pugin, Benoit; Barcik, Weronika; Kurnik-Lucka, Magdalena; Saunders, Ken A; Simpson, Karen D; Schmid-Grendelmeier, Peter; Ferstl, Ruth; Frei, Remo; Sievi, Noriane; Kohler, Malcolm; Gajdanowicz, Pawel; Graversen, Katrine Bækby; Bøgh, Katrine Lindholm; Jutel, Marek; Brown, James R; Akdis, Cezmi A; Hessel, Edith M; O'Mahony, Liam.

In: Nature Communications, Vol. 10, 5711, 2019.

Research output: Contribution to journal › Journal article › Research › peer-review

TY - JOUR

T1 - Obesity and disease severity magnify disturbed microbiome-immune interactions in asthma patients

AU - Michalovich, David

AU - Rodriguez-Perez, Noelia

AU - Smolinska, Sylwia

AU - Pirozynski, Michal

AU - Mayhew, David

AU - Uddin, Sorif

AU - Van Horn, Stephanie

AU - Sokolowska, Milena

AU - Altunbulakli, Can

AU - Eljaszewicz, Andrzej

AU - Pugin, Benoit

AU - Barcik, Weronika

AU - Kurnik-Lucka, Magdalena

AU - Saunders, Ken A

AU - Simpson, Karen D

AU - Schmid-Grendelmeier, Peter

AU - Ferstl, Ruth

AU - Frei, Remo

AU - Sievi, Noriane

AU - Kohler, Malcolm

AU - Gajdanowicz, Pawel

AU - Graversen, Katrine Bækby

AU - Bøgh, Katrine Lindholm

AU - Jutel, Marek

AU - Brown, James R

AU - Akdis, Cezmi A

AU - Hessel, Edith M

AU - O'Mahony, Liam

PY - 2019

Y1 - 2019

N2 - In order to improve targeted therapeutic approaches for asthma patients, insights into the molecular mechanisms that differentially contribute to disease phenotypes, such as obese asthmatics or severe asthmatics, are required. Here we report immunological and microbiome alterations in obese asthmatics (n = 50, mean age = 45), non-obese asthmatics (n = 53, mean age = 40), obese non-asthmatics (n = 51, mean age = 44) and their healthy counterparts (n = 48, mean age = 39). Obesity is associated with elevated proinflammatory signatures, which are enhanced in the presence of asthma. Similarly, obesity or asthma induced changes in the composition of the microbiota, while an additive effect is observed in obese asthma patients. Asthma disease severity is negatively correlated with fecal Akkermansia muciniphila levels. Administration of A. muciniphila to murine models significantly reduces airway hyper-reactivity and airway inflammation. Changes in immunological processes and microbiota composition are accentuated in obese asthma patients due to the additive effects of both disease states, while A. muciniphila may play a non-redundant role in patients with a severe asthma phenotype.

AB - In order to improve targeted therapeutic approaches for asthma patients, insights into the molecular mechanisms that differentially contribute to disease phenotypes, such as obese asthmatics or severe asthmatics, are required. Here we report immunological and microbiome alterations in obese asthmatics (n = 50, mean age = 45), non-obese asthmatics (n = 53, mean age = 40), obese non-asthmatics (n = 51, mean age = 44) and their healthy counterparts (n = 48, mean age = 39). Obesity is associated with elevated proinflammatory signatures, which are enhanced in the presence of asthma. Similarly, obesity or asthma induced changes in the composition of the microbiota, while an additive effect is observed in obese asthma patients. Asthma disease severity is negatively correlated with fecal Akkermansia muciniphila levels. Administration of A. muciniphila to murine models significantly reduces airway hyper-reactivity and airway inflammation. Changes in immunological processes and microbiota composition are accentuated in obese asthma patients due to the additive effects of both disease states, while A. muciniphila may play a non-redundant role in patients with a severe asthma phenotype.

U2 - 10.1038/s41467-019-13751-9

DO - 10.1038/s41467-019-13751-9

M3 - Journal article

C2 - 31836714

VL - 10

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 5711

ER -